Viral-immune interaction in glomerular kidney disease

Project: Research project

Project Details

Description

Viral infection is a major contributor to the global burden of infectious diseases. Virus-related glomerular diseases are seen in increasing frequency in clinical practice but are still underrecognized, thus miss opportunities for timely treatment. Viral exposure can alter host immunity in subtle ways, leaving an indelible footprint on the immune system. While there have been many studies indicating the association of viral infection with glomerular disease, a direct involvement of virus in kidney barrier dysfunction is unknown in most cases. Among remarkable research obstacles, lacking of a convenient and relevant animal model can be the most alarming one. We have recently established a novel mouse model whereby viral proteins drive glomerular disease in concert with a unique immune molecule, soluble urokinase receptor (suPAR). Intranasal injection of SARS-Cov-2 spike S1 protein (2019-nCov) caused proteinuria and podocyte injury specifically in mice with high levels of suPAR. Treatment with anti-suPAR antibody in mice or anti- v 3 integrin antibody on human podocytes blocked proteinuria and protected the glomerular filtration apparatus respectively. Notably, we found this unique synergy between viral protein and host suPAR in causing glomerular disease applies to other integrin binding viruses as well, including HIV-1 and Epstein-Barr virus (EBV). Clinically, suPAR is associated with kidney function loss in patients with HIV-1 infection, and in those with moderate to severe Covid-19. Based on these intriguing new insights, we hypothesize that viral-host suPAR interplay induces glomerular integrin activation and plays an essential role in some virus-associated glomerular disease.
StatusActive
Effective start/end date5/1/242/28/29

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases ( Award #1R01DK13805501): $606,134.00

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